Many investigators affected by sequestration are weighing their options.

Sequestration has not stopped NIH’s National Institute of General Medical Sciences from renewing its Medical Scientist Training Program grant to Harvard Medical School. But the across-the-board federal budget cuts that took effect March 1 reduced from 45 to 40 the number of student slots supported by the program there.

“The absolute number might seem small, but remember that these are highly selected students that represent our biomedical brain trust. That number went down by more than 10% in a single year. This does not bode well for the future of American biomedicine,” observed Thomas Michel, M.D., Ph.D., professor of medicine and biochemistry at Harvard Medical School and a senior physician at Brigham and Women's Hospital.

Dr. Michel was among investigators and others who shared their experiences with GEN about the effect of sequestration on their laboratories. His laboratory studies cardiovascular signal transduction, using biochemical and cell biological approaches to understand the regulation of important cells and molecules in the cardiovascular system. Specifically, the lab focuses on a family of nitric oxide synthase enzymes, which make nitric oxide and control many key pathways in the cardiovascular system.

Since sequestration, Dr. Michel said, his lab has gone from having three active NIH grants to one, serving as principal investigator for a grant that has funded research projects exploring the role of oxidative stress on pathways leading to vascular disease and metabolic abnormalities. NIH’s National Heart, Lung, and Blood Institute awarded $1,756,936 toward “Arterial Dysfunction: Basic and Clinical Mechanisms” for the fiscal year ending September 30—down 4.8% from $1,845,520 in FY 2012. The grant is set to expire in 2015.

“This has influenced, obviously, the scope of my research activities. It has influenced my ability to train new investigators in the field,” Dr. Michel said.

Throwing Away Years of Training

Potential physician scientists, he said, are looking at the challenges of sustaining a viable biomedical research career versus pursuing other careers, perhaps doing more exclusively clinical work: “I think we’re seeing people making difficult decisions, in some cases throwing away years of training in research, because of the uncertainties about continued funding for biomedical research.”

That observation echoes results from a report based on a survey of more than 3,700 science professionals conducted by the American Society for Biochemistry and Molecular Biology (ASBMB) and 15 partnering science groups.

According to “Unlimited Potential, Vanishing Opportunity,” some two-thirds of respondents (65%) said they had difficulties receiving funding, while 55% said they had a colleague who has lost a job or expects to soon, and 46% have laid off scientists or expect to soon. Given such pessimistic findings, the report’s most eye-raising result shouldn’t be too surprising: 18% are considering continuing their scientific career outside the U.S.

“Scientific research cannot survive a stop-and-start funding environment; pauses in research funding often cause scientific results to become unusable sets of data,” the report concluded.

More reassuringly for U.S. biomedical research, the survey found that nearly 95% said they want to continue their careers as scientists. But these days, even starting graduate students are questioning whether they should find some other way to make a living.

Exiting the Lab

“I’m seeing people are who are saying, ‘I’m going to look at science writing. I’m going to look at interesting museums, and use my degree for education, for public information, for other things that are not production of new knowledge, or new scientific products, if you will, such as new drugs or treatments or strategies,” said Huda Akil, Ph.D., co-director and research professor at the Molecular and Behavioral Neuroscience Institute at University of Michigan.

Dr. Akil’s lab studies the neurobiology of emotions, from the molecular level to the brain circuit level in animal models and humans, seeking to understand the brain biology of psychiatric disorders, especially depression and bipolar illness. In May, Dr. Akil and Jun Z. Li, Ph.D., were corresponding authors of a 16-researcher team that in April saw publication in PNAS of their study presenting the first direct evidence of altered circadian rhythms in the brains of people with depression.

U-M is one of five institutions within the Pritzker Neuropsychiatric Disorders Research Fund, which furnished a large part of funding for the study. While the research also benefited from historical funds from NIH’s National Institute of Mental Health, Drs. Akil and Li cobbled together money from numerous other sources.

In addition to the Pritzker fund, these included William Lion Penzner Foundation, the Della Martin Foundation, the National Alliance for Research on Schizophrenia and Depression’s Abramson Family Foundation Investigator Award, an International Mental Health Research Organization—Johnson & Johnson Rising Star Translational Research Award, and two U.S. Office of Naval Research grants (N00014-09-1-059 and N00014-12-1-0366).

New Directions and Opportunities

Also pursuing Department of Defense (DoD) research funding is James M. Wilson, M.D., Ph.D., professor and director of the Gene Therapy Program in the department of pathology and laboratory medicine at University of Pennsylvania, where he is also a professor in the department of internal medicine.

“You can’t go to DoD and ask them to fund fundamental research such as Drosophila genetics. We spend a fair amount of time understanding the strategic priorities of the DoD,” Dr. Wilson said. “Based on this work we conducted some pilot studies to assess feasibility. We then determined whether the kind of research we would be asked to pursue was of interest to our scientists. In the end we found the science interesting and capable of progressing our technology platforms.”

Dr. Wilson’s lab has also stepped up efforts to secure industry sponsors. The lab is close to completing a research agreement with a second company; the first is ReGenX BioSciences, whose NAV™ technology promises faster onset and higher levels of gene expression and longer-lasting gene expression than earlier recombinant AAVs. Dr. Wilson is scientific founder of the company, which holds exclusive worldwide rights to key intellectual property for rAAVs discovered in his lab; UPenn formed ReGenX along with GlaxoSmithKline and Foxkiser.

“What sequestration has forced us to do is be more flexible in the kind of things that we’re doing in the laboratory, which has led to very interesting new directions for our research,” Dr. Wilson said. “Working with these nontraditional sponsors has created some challenges such as more intensive oversight and milestone-driven work plans that can be pulled at any time. The advantages however far outweigh the disadvantages, and have led to opportunities in terms of science and resources.”

While some labs and PIs are able to pursue these opportunities, not all are as fortunate. “The federal government must find a targeted approach to overcome our nation’s debt and deficit problem without harming the investments that invent new technologies, spur economic growth and save American lives,” ASBMB and partners rightly conclude.

That means Washington ending the budget drama that over the past decade has shrunk NIH spending adjusted for inflation 29% since 2003, according to the Federation of American Scientists for Experimental Biology. The House of Representatives doesn’t seem to expect a budget deal until December 15, the end date of yet another temporary spending bill or “continuing resolution” introduced Tuesday by House Appropriations Chairman Hal Rogers (R-KY). Encouragingly, the bill would allow transfers of appropriated-but-unspent “unobligated” funds for biodefense priorities that include funding BARDA research and responding to flu and other pandemics. But the measure would also lock in sequestration cuts, and force the Senate to first vote on defunding Obamacare, both of which Democrats oppose.

In today’s divided Congress, an NIH spending solution will likely await an overall budget agreement that may address other agency issues—the parties are divided on how much social sciences research NIH should fund, for example—or agreements for spending on other agencies. Either is bad news for investigators already scrambling for basic research funds.

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